Impact of the individualization of the first‑line chemotherapy for advanced colorectal cancer based on collagen gel droplet‑embedded drug sensitivity test

Abstract

Abstract. Leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan FOLFIRI) are widely used as first-line chemotherapy regimens in the treatment of advanced colorectal cancer (CRC). However, second-line chemotherapy must be abandoned in certain cases due to disease progression, adverse effects or high medical cost. Therefore, the most effective regimen should be selected as first-line chemotherapy. We reported that individualization of first-line treatment (FOLFOX/FOLFIRI/Dual/Poor responder) was possible using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) and that individualized first-line chemotherapy with CD-DST may improve the prognosis of patients with unresectable CRC. The aim of the present prospective cohort study was to evaluate the individualization of first-line chemotherapy using CD-DST, with a focus on prognosis. Between March 2008 and December 2015, tumor specimens were obtained from 120 patients with CRC who had not received preoperative chemotherapy. CD-DST was performed and the growth inhibition rate (IR) was determined by exposure for 24 h with 5-FU and l-OHP (6.0 and 3.0 µg/ml, respectively) and 5-FU and SN-38 (6.0 and 0.2 µg/ml, respectively). The cumulative distribution of IR values under each condition was evaluated on the basis that the clinical response to FOLFOX and FOLFIRI is equivalent (~50%). The prognosis of dual responder was improved compared with that of poor responders, however this difference was identified to be significant. There was no different prognosis between patients treated with an appropriate first-line regimen and patients treated with an inappropriate first-line regimen in dual responders. However, in poor responders, there were significant differences of prognosis between patients treated with an appropriate first-line regimen and patients treated with an inappropriate first-line regimen (P= 0.036). In conclusion, the results from the present study suggest that administration of the recommended first-line regimen using CD-DST for patients with unresectable CRC is important for the improvement of prognosis, particularly in poor responders.

Effect of oxaliplatin-based chemotherapy on chemosensitivity in patients with peritoneal metastasis from colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: proof-of-concept study

“…Data focusing on the optimization of chemotherapy regimens guided by chemosensitivity testing are seen as controversial, as increased response rates do not necessarily translate into increased survival. A recent study 26 revealed no survival benefit for patients with unresectable colorectal cancer and CD‐DST‐guided first‐line chemotherapy compared with patients who received standard first‐line chemotherapy in a cohort of 120 patients. Interestingly, the subgroup of poor responders to chemotherapy showed significantly improved survival if treated with CD‐DST‐guided first‐line chemotherapy.…”

Sensitivity Assessment of Chemotherapeutic Agents for Ovarian Tumors Based on Test in Vitro Culture: A Blind Study

“…There is no doubt that cell line tests, while enabling high-throughput screening, are not representative of patient-derived tumor tissue. Although the PDX model can simulate the biological characteristics of the tumor, it takes 2-4 months at least [26], and has disadvantages of low implantation e ciency and high cost [27]. 3D tissue block hydrogel culture method preserves the heterogeneity and microenvironment of tumors, and can be used as a method for evaluating tumor drug sensitivity, and the Histoculture drug response assay (HDRA) method [28-30] has gradually used to evaluate clinical drug sensitivity.…”

Impact of primary tumor location as a predictive factor in patients suffering from colorectal cancer treated with cytotoxic anticancer agents based on the collagen gel droplet‑embedded drug sensitivity test

“…Usually, when chemotherapy is performed, patients are monitored for the occurrence and degree of adverse reactions, symptomatic treatment is administered at any time, and symptoms are also managed (26). As we already reported (27)(28)(29), the prognosis of the high-sensitive group is good, so the prediction of adverse reactions is not so important, but it seems to be most important to extract the group that can be expected to be effective.…”

“…Previously, we have reported the effectiveness of CD-DST for the individualization of first-line treatment in CRC. Therefore, the present study aimed to determine the importance of primary tumor location as a predictive factor in cytotoxic anticancer agent treatment using CD-DST (27)(28)(29).…”